Opticin: a potent anti-angiogenic/antiproliferative agent for breast cancer therapy

Introduction

Opticin, a novel extracellular matrix glycoprotein, is a major component of the vitreous humour of the eye. The vitreous humour is one of the few tissues in the body that is avascular and virtually acellular, and previous studies have indicated that opticin contributes to the maintenance of this state by inhibition of angiogenesis. The aim of this present study is to investigate the effect and mode of action of opticin in suppressing tumour cell proliferation and migration in vitro in a panel of breast cancer cell lines and to establish its therapeutic efficacy in human breast tumour xenografts in vivo.

Methods

A replication defective adenoviral vector constitutively expressing human opticin was generated. A panel of breast cancer cell lines were infected with increasing viral doses and effects on cell proliferation and migration were investigated. Inhibition of proliferation was seen in three out of four of the cell lines used in a dose-dependent manner. In MDA-MB-231 cells, increased apoptosis in the virus-treated cells was observed compared with controls. Virally delivered opticin also reduced migration in all the cell lines studied, again in a dose-dependent manner.

Results

To determine whether opticin directly inhibited tumour cell growth in vivo, MDA-MB-231 and MDA-MB-468 cells were implanted intradermally into nude mice and tumours allowed to grow to 200 mm before administration of opticin (10⁸ plaque-forming units). Vessel density was measured by CD31 immunohistochemistry and a reduction of up to 38% was seen compared with untreated controls. A loss of vessel clarity was also observed. Adenoviral opticin-treated tumours were also significantly smaller than controls.

Conclusions

These results demonstrate that opticin has potent anti-angiogenic and anti-proliferative properties both in vitro and in vivo. Together, the current information demonstrates opticin could be considered a novel cancer therapeutic in the treatment of solid tumours.